Percutaneous Fiducial Localization forThoracoscopic Wedge Resection of SmallPulmonary NodulesManu S. Sancheti, MD, Richard Lee, MD, Shair U. Ahmed, MD, Allan Pickens, MD,Felix G. Fernandez, MD, William C. Small, MD, PhD, Sherif G. Nour, MD, andSeth D. Force, MDDepartment of Surgery, Divisions of Cardiothoracic Surgery and General Surgery, and Department of Radiology, Emory University,Emory University Hospital, Atlanta, Georgia

Background. The advent of high-resolution computedtomography scanning and increase in use of chest imag-ing for high-risk patients has led to an increase in theidentification of small pulmonary nodules. The ability tolocate and remove these nodules through a thoracoscopicapproach is difficult. The purpose of this study is toreport our experience with fiducial localization andpercutaneous thoracoscopic wedge resection of smallpulmonary nodules.

Methods. This is a retrospective analysis of ourpatients who underwent computed tomography–guidedfiducial localization of pulmonary nodules. Nodules wereidentified with intraoperative fluoroscopy and removedby thoracoscopic wedge resection.

Results. Sixty-five noduleswere removed in 58 patients.Removal was successful in 98% of patients (57 of 58); 79%of the nodules (53 of 65) were cancers; 20% of these wereprimary lung cancers of which 9 were pure ground-glass

Accepted for publication Feb 4, 2014.

Presented at the Sixtieth Annual Meeting of the Southern ThoracicSurgical Association, Scottsdale, AZ, Oct 30–Nov 2, 2013.

Address correspondence to Dr Sancheti, Emory Clinic Bldg A, Ste 2223,1365 Clifton Rd NE, Atlanta, GA 30322; e-mail: msanch2@emory.edu.

� 2014 by The Society of Thoracic SurgeonsPublished by Elsevier Inc

opacities. Mean size of the nodules was 9.9 ± 4.6 mm(range, 3 to 24 mm). Mean depth from visceral pleuralsurface was 18.7 ± 12 mm (range, 2 to 35 mm). Mean pro-cedure time was 58.7 ± 20.1 minutes (range, 30 to 120), andmean length of stay was 2 days (range, 1 to 6). Complica-tions occurred in 3 patients and included fiducial emboli-zation, fiducial migration, and parenchymal hematoma.Conclusions. Fiducial localization facilitates identifica-

tion and removal of small pulmonary nodules and alle-viates the need for direct nodule palpation. As shown byour series, thoracoscopic wedge resection with fiduciallocalization is an accurate and efficient technique. Thismethod provides a standardized means by which to resectsmall and deep pulmonary nodules or ground-glassopacities.

(Ann Thorac Surg 2014;-:-–-)� 2014 by The Society of Thoracic Surgeons

he increasing use of computed tomography (CT) and

Tthe advent of high-resolution spiral CT has led to anincrease in the detection of subcentimeter pulmonarynodules [1]. In addition, as lung cancer screening pro-grams develop, one can anticipate that the number ofnodules found will grow exponentially [2]. The need todiagnose and treat these nodules cannot be understated.Lung cancer remains the most common cause of cancerdeath, with a dismal overall 5-year survival of 15%.However, the 5-year survival can improve to 60% to 80%with the diagnosis and treatment of early stage cancers[3]. In addition to identifying potential small early lungcancers, subcentimeter nodules requiring diagnosis mayalso be seen in patients with a history of other solid organmalignancies and in patients undergoing transplantevaluations.

Making a specific diagnosis on these lung nodules canbe challenging as their small size may not make themamenable to current nonsurgical modalities, such asimage-guided percutaneous biopsy and transbronchialbiopsy [4]. Surgical resection provides the gold standardfor obtaining a specimen for histopathologic diagnosis,and video-assisted thoracic surgery or thoracoscopy al-lows the resection to be performed with minimally inva-sive techniques. Unfortunately, traditional video-assistedthoracic surgery techniques are limited by the need topalpate the lung to isolate the appropriate area of resec-tion, which can make it very difficult to identify andremove small, deep, nonpalpable lesions [5].Suzuki and colleagues [6] found that in their series of

cases in which thoracoscopy was converted to thoracot-omy, 46% were due to the inability to localize nodules.This percentage increases to 63% if the nodule is less than10 mm or greater than 5 mm from the pleural surface [6].

Dr Pickens discloses a financial relationship withEthicon Endosurgery.

0003-4975/$36.00http://dx.doi.org/10.1016/j.athoracsur.2014.02.028

2 SANCHETI ET AL Ann Thorac SurgFIDUCIAL LOCALIZATION OF SMALL PULMONARY NODULES 2014;-:-–-

A variety of localization methods have been developed toattempt to solve this dilemma, ranging from thoraco-scopic ultrasonography [7–9], percutaneous hook wires[5], percutaneous coils [10], contrast/dyes [11, 12], radio-tracers [13], and bronchoscopically placed localizers[14, 15]. All of these techniques include various limita-tions and complications.

Another technique for lung nodule localization in-volves the placement of a 3-mm gold fiducial marker in ornear the nodule or nodules of interest. These markers areplaced preoperatively, adjacent to the culprit lesions, byutilizing CT guidance. Intraoperative fluoroscopy canthen be used to identify the fiducial marker, which is thenused as a surrogate for the nodule and facilitates thewedge resection of the lesion of interest. This study wasdesigned to analyze the reliability, safety, and feasibilityof this technique at our institution.

Patients and Methods

This study was performed as a retrospective review of ourthoracic surgical database and was approved by ourInstitutional Review Board. Owing to the retrospectivenature of this study and lack of patient-specific identifiers,individual patient consent was waived. From April 2011 toMay 2013, 58 patients (22 female) underwent thoraco-scopic resection of 65 pulmonary nodules with fiduciallocalization at Emory University Hospital.

Image-Guided Fiducial Placement TechniquePreoperatively, the fiducial marker was placed in theinterventional radiology department with local anes-thesia. With the assistance of CT guidance, a 1.2 � 3 mmgold fiducial marker, depicted in Figure 1 (CIVCO Med-ical Solutions, Coralville, IA), was placed in appropriateposition to mark the lesion of interest. The marker wasplaced through a coaxial 17G needle with the markerrecessed within the lumen proximal to the tip. An internalstylet was used to push the marker beyond the introducertip to accomplish delivery immediately adjacent to theculprit lesion. After positioning was achieved and themarker delivered, repeat imaging documented finalfiducial positioning with respect to the lesion as a finalguide for surgical removal. The localization procedurewas performed on the same day of the thoracoscopicsurgery except in 2 cases.

Fig 1. Gold fiducial marker, 1.2 � 3 mm (CIVCO Medical Solutions,Coralville, IA).

Operative TechniqueThe CT images after fiducial placement were reviewed bythe surgeon before resection to determine the location ofthe fiducial marker relative to the nodule. A representa-tive CT image after fiducial placement is shown inFigure 2. Standard thoracoscopy positioning, monitoring,and anesthesia were employed in 35 cases, and in 23cases, isolated lung ventilation was not utilized. We havepreviously described this technique [16]. Thoracoscopywas performed utilizing two 5-mm trocars and one12-mm trocar. Intraoperative fluoroscopy was used tolocate the fiducial marker, and the adjacent lung wasgrasped and elevated. A representative fluoroscopy im-age with fiducial marker in place is shown in Figure 3.Wedge resection of the lung parenchyma containing thefiducial marker was performed with an endoscopic sta-pler in standard fashion. Excision of the fiducial markerwas confirmed with fluoroscopy and frozen section.

Data Collection and AnalysisThe medical records of the patients were reviewed. Thedemographics and body mass index were collected.Fluoroscopy time and total operating room time wererecorded. From pathology, the size, depth, and histologyof the nodules were tabulated. Complications and lengthof stay were also identified. Data are reported as meanvalue with standard error.

Results

Sixty-five nodules were removed in 58 patients, 22 ofwhom were female (44%). The mean patient age was 55years (range, 24 to 80), and the average body mass indexwas 29.6 � 6.9 kg/m2 (range, 20 to 50 kg/m2). Forty-six(79%) of the patients presented with a history of cancer.Three pneumothoraces (5%) were found immediately

after the fiducial placement and treated with a pleuraldrain without complications. Fiducial marker and adjacent

Fig 2. Computed tomography image after fiducial placement (arrow).

Fig 3. Intraoperative fluoroscopy image with fiducial marker in place(arrow).

Table 2. Pathology of Nodules

Pathology No. of Nodules

Adenocarcinoma, lung primary 13Metastatic colon cancer 12Metastatic melanoma 6Metastatic squamous cell carcinoma, not lung 6Metastatic hepatocellular carcinoma 5Benign lymph node 5Metastatic renal cell carcinoma 4Carcinoid 2Inflammation 2Pneumonia 2Metastatic thyroid carcinoma 2Metastatic adenoid carcinoma 1Metastatic cholangiocarcinoma 1Metastatic angiosarcoma 1Granuloma 1Hamartoma 1Scar 1

3Ann Thorac Surg SANCHETI ET AL2014;-:-–- FIDUCIAL LOCALIZATION OF SMALL PULMONARY NODULES

nodule removal was successful in 57 patients (98%). In 1patient, the nodule was determined to be too deep forwedge resection, and the patient ultimately underwentlobectomy for removal of the lesion. Six procedures(10.3%) were ipsilateral reoperations after previous lungresections. No operations were converted to thoracotomy.

The characteristics of the nodules are shown in Table 1.The mean size of the nodules was 9.9 � 4.6 mm (range, 3to 24 mm), and the mean distance from the pleural sur-face to the nodule was 18.7 � 12 mm (range, 2 to 35 mm).Pathologic diagnosis of the nodules is shown in Table 2.Fifty-three nodules (79%) were found to be malignant,with 13 (20%) representing primary lung cancers. Elevennodules (17%) were pure ground-glass opacities (GGO),and 9 of these GGO lesions were found to be primarylung cancers.

The average operative time was 58.7 � 20.1 minutes(range, 30 to 120), including a mean fluoroscopy timeof 10 � 21.8 minutes. The length of stay for this group ofpatients ranged from 1 day to 6 days, with an averageof 1.8 � 1.2 days.

Three complications (5%) were noted in our patientpopulation. These complications included fiducialembolization, fiducial migration, and parenchymal he-matoma. In all 3 patients, the respective nodule wassuccessfully removed despite the complications.

Table 1. Characteristics of Lung Nodules

Size(9.9 � 4.6 mm)No. ofNodules Depth(18.7 � 12 mm)

No. ofNodules

0–5 mm 13 0–10 mm 215–10 mm 26 10–20 mm 1710–15 mm 20 20–30 mm 17>15 mm 6 >30 mm 10

Comment

Increased utilization of high-resolution computed to-mography and the implementation of lung cancerscreening programs have led to a significant rise in theprevalence of indeterminate lung nodules [1, 2]. Thor-acoscopy has been progressively defined as an efficientmeans to provide pathologic diagnosis of these nodules,with possible concurrent definitive resection. Unfortu-nately, these nodules can often be subcentimeter in size,deep in the pulmonary parenchyma, and varied intexture, thus precluding the ability to isolate them bystandard thoracoscopic techniques of finger palpation [5].Preoperative localization techniques provide a clear

benefit as an aid to sublobar pulmonary resection in thispopulation as well as in patients requiring metastatec-tomies. Several studies have documented specific in-dications in which localization techniques should beemployed. As previously stated, Suzuki and colleagues [6]recommend that localization techniques be used whenthe nodules are less than 10 mm in size or more than5 mm from the visceral pleural surface or both [6].Nakashima [17] developed three criteria: (1) nodulediameter of 5 mm or less; (2) ratio of maximum diameterof nodule to minimum distance between pleural surfaceand inferior border of nodule is less than or equal to 0.5;and (3) nodule is of low density on computer tomography.The authors [16] recommended that localization tech-niques be used if two or more of these criteria are met.Saito and coworkers [18] determined that a linear func-tion (depth ¼ 0.836 � size � 2.811) could differentiatebetween nodules requiring localization and those that donot.Several localization techniques have been developed to

provide a means to isolate pulmonary nodules duringthoracoscopy. Each one includes its own advantages andlimitations. The percutaneous image-guided placement of

4 SANCHETI ET AL Ann Thorac SurgFIDUCIAL LOCALIZATION OF SMALL PULMONARY NODULES 2014;-:-–-

hook wires or microcoils involve a morbidity rate as highas 15% including the risk of pneumothorax, pulmonaryhemorrhage, and significant pleural pain [5, 19]. Also,the hook wire technique carries the increased risk ofsystemic air embolism [5]. Additionally, surgeons havefound that in the case of a pneumothorax the hook wirecan pull out of the lung parenchyma, nulling the benefitits placement. Intraoperative imaging, such as thoraco-scopic ultrasonography, has been shown to require com-plete lung collapse for accurate imaging, which may provequite difficult with emphysematous lungs or those withpleural adhesions [7, 8]. Various endoscopically or percu-taneously placed injectable markers have been used, suchas barium, methylene blue, colored collagen, and lipiodol[11, 12, 14, 15]. Dyes have a risk of parenchymal diffusionafter placement and thus are difficult to visualize uponthoracoscopy, especially in anthracotic lungs [20]. Bariumand lipiodol are water insoluble and carry the risk of em-bolism [11]. The risk of anaphylaxis to any injectable sub-stance is also present [21]. Finally, few groups have studiedthe use of radiotracers as markers similar to those used inbreast surgery. This technique is limited by fast diffusion ofthe contrastmedium and the inability of the probe to detectdeeper and posterior nodules [9, 13].

This study retrospectively reviews the Emory Univer-sity data regarding our localization technique of utilizingCT-guided placement of 3-mm gold fiducial markersadjacent to the nodules. This method of tumor marking isalso used by interventional radiologists and radiationoncologists in pretreatment marking and tumor trackingbefore radiotherapy and has been found to be safe andeffective [22]. Because the marker is placed with CTguidance, the CT imaging is used to help determine theposition of the nodule in relation to the marker. Thatpresents a distinct advantage over bronchoscopicallyplaced markers where it can be difficult to identifywhether the nodule is deep to, above, or below themarker. Additionally, in 3 of our patients, the procedurewas canceled when the CT imaging used for fiducialplacement showed resolution of the nodule in question.The fiducial marker is located with standard intra-operative fluoroscopy and resected with the adjacentnodule thoracoscopically, and therefore, after resection,the specimen itself can be visualized under fluoroscopy toensure inclusion of the fiducial marker.

This technique was used in 58 patients with an excel-lent success rate of 98%. Failure rates among previouslypublished localization techniques range from 0% to 47%[8, 10]. Very small and deep nodules were able to beremoved, and the procedure could be employed in largepatients, who present a particular challenge when tryingto identify lung nodules. The mean nodule size of 9.9 �4.6 mm and mean depth of 18.7 � 12 mmwere well withinthe proposed indications for utilization of localizationtechniques previously mentioned. In the isolated unsuc-cessful case, the nodule was too central and close to thepulmonary artery for safe wedge resection. In this case,the fiducial was removed, but the nodule was left behind,and the patient later underwent an uncomplicated thor-acoscopic lobectomy for resection of the nodule.

Inherent advantages of this method include the abilityto perform the resections with routine thoracoscopic in-struments and standard operative fluoroscopy. No specialinstrumentation is needed. In our institution, two 5-mmtrocars and one 12-mm trocar were utilized. Using stan-dard thoracoscopic practices, we were able to performcases that may have been limited by specialized equip-ment, instruments, or markers. For example, 10.3% ofour cases were ipsilateral reoperations with significantpleural adhesions. The operative duration and post-operative length of stay are comparable to standardcontrols for thoracoscopy, and the use of fluoroscopy waskept to a minimum (mean 10.1 minutes) to lessen patientand staff exposure.The fiducial marker is only 3 mm, and its associated

delivery system is equally small. That minimizes the levelof trauma to the pulmonary parenchyma, as evidenced bya low pneumothorax rate of 5%. Of note, all pneumo-thoraces were recognized immediately after fiducialmarker placement on postprocedure CT scan. A chesttube was placed, and the patient was transferred to theoperating room for subsequent thoracoscopy. The fiducialmarker is constructed of gold, an inert element so the riskof allergic reaction is negligible, and it can remain in thepulmonary parenchyma without risk of reaction. There-fore, the timing between placement and resection can bevariable. In our series, owing to patient scheduling con-venience, all except two resections were performedimmediately after fiducial marker placement. The twoexceptions were performed the day after marker place-ment. In addition, because of its inert properties, thefiducial marker has very little effect on the surroundingtissue and subsequent histopathologic analysis [23].Our technique proved be an efficient method to

remove and diagnose a variety of pathologies. Seventy-nine percent of the nodules were found to malignant onpathology. Thirteen (20%) of these malignant lesionsproved to be a primary lung cancer. Of note, our seriesshowed the ability to resect pure GGO lesions, a radio-graphic finding that is difficult to isolate and resectthoracoscopically. Nine of these pure GGO lesions werediscovered to be primary lung cancer. A definitiveresection was performed during the same operation onpatients found to have a primary lung malignancy. Allmargins were oncologically adequate for patients un-dergoing metastatectomies. By detecting and resectingthese small malignant nodules early, the goal is to pro-vide the patients the highest chance of cure [24].Three complications (5%) were noted in our patient

population. These complications included fiducial em-bolization, fiducial migration, and parenchymal hema-toma. In 1 case, early in our experience, a marker wasinadvertently deployed in an inferior pulmonary vein andfound to have migrated over the ventral aspect of theheart near the apex during localization. An urgent echo-cardiogram was performed that demonstrated the markerto have embolized into the left anterior descendingartery. The patient was admitted for observation but wasasymptomatic with normal cardiac enzymes. No furtherintervention was indicated, and the patient recovered

5Ann Thorac Surg SANCHETI ET AL2014;-:-–- FIDUCIAL LOCALIZATION OF SMALL PULMONARY NODULES

without incident. She subsequently returned later forthoracoscopic resection of her nodule using fluoroscopicguidance by means of an additional fiducial markerplaced at the initial localization procedure. Long-termfollow-up with her cardiologist yielded no adversesequelae, and she is maintained on antiplatelet therapy.In another patient, the marker was found to havemigrated from the parenchyma into the pleural space.Fortunately, the track formed from the fiducial markerplacement isolated the area of interest for resection, andthe nodule was successfully removed. Finally, a superfi-cial parenchymal hematoma was noted to have devel-oped in 1 patient after placement of the marker. Thefinding was clinically insignificant, and the hematomawas removed along with the nodule at time of surgery.

A limitation of this series and technique is that it was aretrospective review of patients undergoing a specificprocedure in one institution, with the bias inherent in allretrospective studies. This model also leads to an elementof selection bias. Next, the methodology requires thecoordination of the patient, the thoracic surgeon, theinterventional radiologist, and the fluoroscopy technician.The utilization of multiple specialties does add to theexpense and complexity of the procedure. However,surgeons at some institutions do perform their owninterventional procedures, which could make the flow ofsteps much smoother. Ideal future studies would involvea prospective and randomized model that analyzes thevarious techniques of localization.

Withmodern imagingmodalities, the discovery of small,deep, and nonpalpable pulmonary nodules is inevitable.The indication for the applicationof localization techniquesin thoracoscopy has become clearer, and several methodsof localization have been developed. Our techniquedemonstrated an excellent success rate with a lowmorbidity rate in the resection of lesions that meet thecurrent indications for size and depth. A wide array of pa-thology was present in the specimens, including a largeproportion of malignancies, especially consisting of theelusive pure GGO. Overall, our technique of using CT-guided placement of fiducial markers and subsequentresection with intraoperative fluoroscopy can safely andreliably contribute to the thoracic surgeon’s armamen-tarium inmanaging small, deep, andnonpalpable nodules.

References

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2. Kaneko M, Eguchi K, Ohmatsu, et al. Peripheral lung cancer:screening and detection with low-dose spiral CT versusradiography. Radiology 1996;201:798–802.

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4. Li H, Boiselle PM, Shepard JO, et al. Diagnostic accuracy andsafety of CT-guided percutaneous needle aspiration biopsyof the lung: comparison of small and large pulmonary nod-ules. AJR Am J Roentgenol 1996;167:105–9.

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7. Kondo R, Yoshida K, Hamanaka K, et al. Intraoperative ul-trasonographic localization of pulmonary ground-glassopacities. J Thorac Cardiovasc Surg 2009;138:837–42.

8. Santambrogio R, Montorsi M, Bianchi P, et al. Intraoperativeultrasound during thoracoscopic procedures for solitarypulmonary nodules. Ann Thorac Surg 1999;68:218–22.

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10. Powell TI, Jangra D, Clifton JC, et al. Fluoroscopically guidedvideo-assisted thoracoscopic resection after computedtomography-guided localization using platinum microcoils.Ann Surg 2004;240:481–9.

11. Watanabe K, Nomori H, Ohtsuka T, et al. Usefulness andcomplications of computed tomography-guided lipiodolmarking for fluoroscopy-assisted thoracoscopic resection ofsmall pulmonary nodules: experience with 174 nodules.J Thorac Cardiovasc Surg 2006;132:320–4.

12. Nomori H, Hirotoshi H. Colored collagen is a long-lastingpoint marker for small pulmonary nodules in thoracoscopicoperations. Ann Thorac Surg 1996;61:1070–3.

13. Bellomi M, Veronesi G, Trifiro G, et al. Computedtomography-guided preoperative radiotracer localizationof nonpalpable lung nodules. Ann Thorac Surg 2010;90:1759–65.

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DISCUSSION

DR TRAVES CRABTREE (St. Louis, MO): We saw a paper earliertoday where the benign resection rate was around 12%, our benignresectionrateatWashUisabout 12%, I thinkwe just sawa talk in thelast session where it was around 25%, and yours is around 21%. Doyou think the ability to do this makes it the right thing to do?

DR SANCHETI: Thank you for your question. The appropriateclinical scenario dictates the usefulness of this approach. Many ofthe patients that were recommended to undergo resection in ourseries were preoperative solid organ transplant patients andthose with a history of nonpulmonary malignancies that werefound to have small pulmonary nodule. Although many lesionswere benign, I do think if we are able to isolate/resect/diagnosesmall lesions in patients of these clinical scenarios, we candrastically alter their treatment plan. Therefore, I do think it is auseful approach in the right situation.

DR ROBERT J. CERFOLIO (Birmingham, AL): Congratulations.Good technique. How much radiation is the patient getting andhow much radiation are your hands getting and do you weargloves while you are doing it? Lead gloves? Your hands are beingexposed to radiation.

DR SANCHETI: Thank you, Dr Cerfolio. We do not wearspecialized gloves, but do take standard precautionary measureswith fluoroscopy. Specifically, Dr Cerfolio, in terms of the fluo-roscopy time, we had a few extremes, but if you take out theextremes, our times calculates to about 3.1 minutes.

DR DARRYL S. WEIMAN (Memphis, TN): My question is, youfind one of these little cancers and it’s consistent with a lungprimary. Now what do you do?

DR SANCHETI: That’s a goodquestion. Thankyou. Ifwedofindaprimary lung cancer in these lesions, we perform a lymph nodedissection at that time. The definitive, anatomic resection dependson the clinical situation of the patient. Like previously discussed, afew of these patients had other nonpulmonary malignancies, andsome were pretransplant workups. If clinically appropriate and ifthe patient could tolerate a lobectomy or a segmentectomy, thenwe would go ahead and do that either at that time or later on.

DR JOSHUA ROBERT SONETT (New York, NY): Excellenttechnique and I think it’s complementary to the one we sawearlier. There is no reason that when you are putting the blue dyein you could also put a fiducial in so the blue dye would mark thesurface and a fiducial would mark the depth. So I think they’recomplementary and you may be able to do it all in one settingwithout the percutaneous needle biopsy. And, too, again, I wouldjust encourage everybody to, for nonmetastatic patients ortransplants, use the NCCN guidelines or the AATS or the Chestguidelines for when we should approach and seriously considerresecting nodules, because we shouldn’t be taking out all of thesejust because we can.

DR MITCHELL MAGEE (Dallas, TX): One quick comment. I justwanted to say that I have used a similar technique with a fiducialmarker that is radiopaque but not used intraoperative fluoros-copy as liberally as you have but to just take an X-ray film of itwhen you get it out, because sometimes you may not be able tosee it quite as easily, and if you have got your specimen out andX-ray film it and your fiducial is in there, then you know youhave gotten a lesion.

DR SANCHETI: I appreciate that comment and approach.

DR WILLIAM BOLTON (Greenville, SC): Just a comment onthe podium’s last statement. So, yes, putting a fiducial marker inthere with this navigational bronchoscopy would be quite easy.It would take you very little time, about less than a minute, toadd that to your original procedure. So it certainly could bedone.

DR M. BLAIR MARSHALL (Washington, DC): Can you providethe cost of the fiducial?

DR SANCHETI: I unfortunately do not know the cost of thefiducial.

DR DOUGLAS MINNICH (Birmingham, AL): The gold seedsare approximately $50. I was going to talk about some of this inthe next presentation, but some of the other fiducials are in the$150 to $175 range.